The rapid conduction of action potentials in both the central nervous system (CNS) and peripheral nervous system (PNS) depends on the formation of a myelin sheath around neuronal axons. In the PNS, myelination initiation requires an interaction between Schwann cells and an individual axon, a process known as radial sorting [1]. During myelination, Schwann cells form an insulating, multilamellar sheath around associated axonal segments, resulting in the formation of four specialized domains: the internode, the juxtaparanode, the paranodal region and the Node of Ranvier. In the internode, axons are ensheathed by compact myelin consisting of the Schwann cell membrane and expressed myelin basic protein (MBP). The juxtaparanodal region sits adjacent to the paranode and contains localized clusters of voltage-gated potassium channels (vgpc's) in the axon. In the paranodal region, the axon and myelin sheath form axo-glial junctions where Schwann cells express neurofascin 155 form heterodimers along with axonal protein contactin-associated protein (CASPR) [2]. At the Nodes of Ranvier, which are specialized regions of unmyelinated axon between two myelin segments, the presence of clusters of voltage-gated sodium channels (vgsc's) facilitate the saltatory conduction of action potentials [3].
Model systems that can represent the myelination of motoneurons by glial cells have previously proven difficult to develop. Myelination of neurons by Schwann cells has been extensively studied using dorsal root ganglia (DRG) cultures in a variety of serum containing and serum-free in vitro systems [4]. However, while many groups have reported the successful co-culture of primary motoneurons and Schwann cells, the success of myelinating sensory neuron systems has not been translated to motoneuron systems [5-10]. The development of a functional myelinating motoneuron/Schwann cell system is a necessary first step in describing the molecular events surrounding the interactions between these cells that have myelination as the end result. Additionally, such a system would benefit scientists' ability to study both central and peripheral demyelinating neuropathies such as multiple sclerosis, Guillain-Barré Syndrome, diabetes associated peripheral neuropathies and progressive muscular atrophy, under controlled conditions. Previous studies have described methods to create defined systems to understand hippocampal function [11] and motoneuron regeneration [12]. The adaptation of these culture systems to motoneurons/Schwann cell co-culture would be an ideal solution to this problem.